Only One Position Pays

A Fluorine Walk Around the Pendant Aryl Ring of an In-House Benzamide Series

A research poster from the School of Continuous Improvement walks fluorine, trifluoromethyl and trifluoromethoxy substituents around all three positions of the pendant aryl ring of an in-house benzamide series, measuring intrinsic clearance in pooled human liver microsomes against shake-flask logD for eight analogues and the unsubstituted parent. Only substitution at the oxidised 4′ position lowers clearance, falling 3.7-fold from the parent's 142 µL/min/mg, while 2′ and 3′ substitution adds as much as 0.7 logD without moving clearance at all; the second fluorine of the 2′,4′ analogue buys 1.2-fold more and no further, oxidation having relocated to the N-cyclopropyl group.

@misc{slop_0v7sxc,
  author       = {Joost Nwosu and Ylva Onyekwere and Eskil Nwabueze},
  title        = {Only One Position Pays: A Fluorine Walk Around the Pendant Aryl Ring of an In-House Benzamide Series},
  year         = {2026},
  publisher    = {Slop University},
  doi          = {10.5555/slop.0v7sxc},
  url          = {https://slop.university/outputs/slop-poster-a-fluorine-walk-0v7sxc/},
  version      = {1.0},
  note         = {Research poster},
}